The purpose of this project is to determine the mechanism by which senescent human red blood cells (RBC) and RBC stored in vitro for transfusion are removed from the circulation. Previous experiments performed in this laboratory suggest that macrophages distinguish autologous senescent from mature RBC on the basis of selective IgG attachment to the former. The Ig eluted from senescent cells and RBC stored as whole blood was shown to be an IgG free of other Ig's by immunodiffusion, immunoelectrophoresis and polyacrylamide gel electrophoresis. The IgG eluted from senscent cells reattached to homologous cells by the Fab region as determined by receptor blockade studies and immunoelectron microscopy, and initiated their phagocytosis by macrophages. Thus, the IgG which attaches to senescent cells in situ appears to be an autoantibody which contributes to the maintenance of homeostasis by initiating the removal of senescent and stored cells. Experiments suggest that this IgG may limit the transfusion effectiveness of blood cells by binding to them during storage.